An assessment of the analytical performance of non‐invasive prenatal testing (NIPT) in detecting sex chromosome aneuploidies: 34,717‐patient sample in a single prenatal diagnosis centre in China

Abstract Background Since the discovery of cell-free DNA (cfDNA) in maternal plasma, it has opened up new approaches for non-invasive prenatal testing. With the development of whole-genome sequencing, small subchromosomal deletions and duplications could be found by NIPT. This study is to review the efficacy of NIPT as a screening test for aneuploidies and CNVs in 42,910 single pregnancies. Methods A total of 42,910 single pregnancies with different clinical features were recruited. The cell-free fetal DNA was directly sequenced. Each of the chromosome aneuploidies and the subchromosomal microdeletions/microduplications of PPV were analyzed. Results A total of 534 pregnancies (1.24%) were abnormal results detected by NIPT, and 403 pregnancies had underwent prenatal diagnosis. The positive predictive value (PPV) for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), and other chromosome aneuploidy was 79.23%, 54.84%, 13.79%, 33.04%, and 9.38% respectively. The PPV for CNVs was 28.99%. The PPV for CNVs ≤ 5 Mb is 20.83%, for within 5–10 Mb 50.00%, for > 10 Mb 27.27% respectively. PPVs of NIPT according to pregnancies characteristics are also different. Conclusion Our data have potential significance in demonstrating the usefulness of NIPT profiling not only for common whole chromosome aneuploidies but also for CNVs. However, this newest method is still in its infancy for CNVs. There is still a need for clinical validation studies with accurate detection rates and false positive rates in clinical practice.

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Incidental Prenatal Diagnosis of Sex Chromosome Aneuploidies: Health, Behavior, and Fertility

ISRN Obstetrics and Gynecology ◽

10.5402/2011/807106 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 23

Author(s):

J. J. P. M. Pieters ◽

A. J. A. Kooper ◽

A. Geurts van Kessel ◽

D. D. M. Braat ◽

A. P. T. Smits

Keyword(s):

Prenatal Diagnosis ◽

Reproductive Health ◽

Prognostic Value ◽

Sex Chromosome ◽

Prenatal Testing ◽

Cochrane Library ◽

Medical Subject Headings ◽

The Cochrane Library ◽

Chromosomal Aneuploidies ◽

Sex Chromosome Aneuploidies

Objective. To assess the diagnostic relevance of incidental prenatal findings of sex chromosome aneuploidies. Methods. We searched with medical subject headings (MeSHs) and keywords in Medline and the Cochrane Library and systematically screened publications on postnatally diagnosed sex chromosomal aneuploidies from 2006 to 2011 as well as publications on incidentally prenatally diagnosed sex chromosomal aneuploidies from 1980 to 2011. Results. Postnatally diagnosed sex chromosomal aneuploidies demonstrated three clinical relevant domains of abnormality: physical (22–100%), behavior (0–56%), and reproductive health (47–100%), while incidentally prenatally diagnosed sex chromosomal aneuploidies demonstrated, respectively, 0–33%, 0–40%, and 0–36%. Conclusion. In the literature incidental prenatal diagnosis of sex chromosomal aneuploidies is associated with normal to mildly affected phenotypes. This contrasts sharply with those of postnatally diagnosed sex chromosomal aneuploidies and highlights the importance of this ascertainment bias towards the prognostic value of diagnosis of fetal sex chromosomal aneuploidies. This observation should be taken into account, especially when considering excluding the sex chromosomes in invasive prenatal testing using Rapid Aneuploidy Detection.

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SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy

Prenatal Diagnosis ◽

10.1002/pd.4159 ◽

2013 ◽

Vol 33 (7) ◽

pp. 643-649 ◽

Cited By ~ 83

Author(s):

Carole Samango-Sprouse ◽

Milena Banjevic ◽

Allison Ryan ◽

Styrmir Sigurjonsson ◽

Bernhard Zimmermann ◽

...

Keyword(s):

Sex Chromosome ◽

Prenatal Testing ◽

High Accuracy ◽

Non Invasive ◽

Sex Chromosome Aneuploidies

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Cell-free DNA screening for sex chromosome aneuploidies by non-invasive prenatal testing in maternal plasma

Molecular Cytogenetics ◽

10.1186/s13039-020-0478-5 ◽

2020 ◽

Vol 13 (1) ◽

Cited By ~ 2

Author(s):

Yipeng Wang ◽

Shanshan Li ◽

Wei Wang ◽

Yuan Dong ◽

Meng Zhang ◽

...

Keyword(s):

Sex Chromosome ◽

Prenatal Testing ◽

Maternal Plasma ◽

Cell Free Dna ◽

Non Invasive ◽

Free Dna ◽

Sex Chromosome Aneuploidies

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Prenatal diagnosis and pregnancy determination of sex chromosome aneuploidy screened by non-invasive prenatal testing from 52,453 unselected singleton pregnancies: a retrospective analysis of 4-year experience

10.21203/rs.2.21260/v2 ◽

2020 ◽

Author(s):

Xiaojin Luo ◽

Liang Hu ◽

Yuanyuan Pei ◽

Xiaoyi Cong ◽

Xiaoyi Liu ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Sex Chromosome ◽

Prenatal Testing ◽

Low Risk ◽

True Positive ◽

Sex Chromosome Aneuploidy ◽

Non Invasive ◽

Selective Population ◽

Ultrasound Findings ◽

Singleton Pregnancies

Abstract Objective To estimate the positive predictive value (PPV) of fetal sex chromosome aneuploidy (SCA) screened in non-selective population and explore the rate of pregnancy termination and ultrasound findings for fetal SCA and the factors influencing parents’ decisions in South China. Methods This is a large-scale retrospective cohort of positive SCA screened from unselected singleton pregnancies by non-invasive prenatal testing (NIPT) from a single prenatal center of a tertiary hospital, from January 2016 to November 2019. Clinical information, indications, diagnostic results, ultrasound findings, pregnancy determinations, and follow-up were reviewed and analyzed. Results 248 cases of SCA positive were screened out of 52453, giving a positive detection rate of 0.47%. The majority of indications (42.7%) were low-risk pregnancies. After genetic counseling, 43 pregnancies (17.3%) declined to prenatal diagnosis, the rest of 205 cases (82.7%) conducted with amniocentesis to detect fetal chromosome, of which 95 were confirmed as true positive of SCA with PPV of 46.3% (95/205). The SCA consisted of 68 sex chromosomal trisomies (26 cases of 47,XXY, 20 cases of 47,XXX and 22 cases of 47,XYY), 17 cases of monosomy X (45,X), three cases of 48,XXYY, three cases of mosaicisms (45,X/46,XX), four cases with sex chromosomal deletions, included two cases of 46,X,del(Y)(q11.21), one case of 46,X,del(X)(p11) and one case of 46,X,i(X)(q10). Of the 95 cases confirmed as true positive SCA, 50 cases (52.6%)chose to terminate the pregnancy (82.6%, 64.3%, 17.6% and 33.3% for 45,X, 47,XXY, 47,XXX and 47,XYY, respectively), 45 cases (47.4%) elected to continue the pregnancy. Ninety-three pregnant were also continued pregnancy after the exclusion of SCA. Conclusions NIPT, as a first-tier routine method for screening autosomal aneuploidies, also could play an important role in screening SCA. Low-risk pregnant women are the main indication for the detection of SCA as NIPT test provides to non-selective population. The trend of overall termination rates of SCA-affected pregnancies is decreased. For 47,XXX and 47,XYY with mild phenotype, couples would like to continue the pregnancy. But for 45,X and 47,XXY, parents apt to terminate pregnancy no matter ultrasound abnormalities were found or not. pregnancy determinations are affected by types of SCA, sonographic findings, maternal age, and presence of infertility.

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Prenatal diagnosis and pregnancy determination of sex chromosome aneuploidy screened by non-invasive prenatal testing from 52,453 unselected singleton pregnancies: a retrospective analysis of 4-year experience

10.21203/rs.2.21260/v1 ◽

2020 ◽

Author(s):

Xiaojin Luo ◽

Liang Hu ◽

Yuanyuan Pei ◽

Xiaoyi Cong ◽

Xiaoyi Liu ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Sex Chromosome ◽

Prenatal Testing ◽

Low Risk ◽

True Positive ◽

Sex Chromosome Aneuploidy ◽

Non Invasive ◽

Selective Population ◽

Ultrasound Findings ◽

Singleton Pregnancies

Abstract Objective To estimate the positive predictive value (PPV) of fetal sex chromosome aneuploidy (SCA) screened in non-selective population and explore the rate of pregnancy termination and ultrasound findings for fetal SCA and the factors influencing parents’ decisions in South China.Methods This is a large-scale retrospective cohort of positive SCA screened from unselected singleton pregnancies by non-invasive prenatal testing (NIPT) from a single prenatal center of a tertiary hospital, from January 2016 to November 2019. Clinical information, indications, diagnostic results, ultrasound findings, pregnancy determinations, and follow-up were reviewed and analyzed.Results 248 cases of SCA positive were screened out of 52453, giving a positive detection rate of 0.47%. The majority of indications (42.7%) were low-risk pregnancies. After genetic counseling, 43 pregnancies (17.3%) declined to prenatal diagnosis, the rest of 205 cases (82.7%) conducted with amniocentesis to detect fetal chromosome, of which 95 were confirmed as true positive of SCA with PPV of 46.3% (95/205). The SCA consisted of 68 sex chromosomal trisomies (26 cases of 47,XXY, 20 cases of 47,XXX and 22 cases of 47,XYY), 17 cases of monosomy X (45,X), three cases of 48,XXYY, three cases of mosaicisms (45,X/46,XX), four cases with sex chromosomal deletions, included two cases of 46,X,del(Y)(q11.21), one case of 46,X,del(X)(p11) and one case of 46,X,i(X)(q10). Of the 95 cases confirmed as true positive SCA, 50 cases (52.6%)chose to terminate the pregnancy (82.6%, 64.3%, 17.6% and 33.3% for 45,X, 47,XXY, 47,XXX and 47,XYY, respectively), 45 cases (47.4%) elected to continue the pregnancy. Ninety-three pregnant were also continued pregnancy after the exclusion of SCA.Conclusions NIPT, as a first-tier routine method for screening autosomal aneuploidies, also could play an important role in screening SCA. Low-risk pregnant women are the main indication for the detection of SCA as NIPT test provides to non-selective population. The trend of overall termination rates of SCA-affected pregnancies is decreased. For 47,XXX and 47,XYY with mild phenotype, couples would like to continue the pregnancy. But for 45,X and 47,XXY, parents apt to terminate pregnancy no matter ultrasound abnormalities were found or not. pregnancy determinations are affected by types of SCA, sonographic findings, maternal age, and presence of infertility.

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Clinical Experience with Fetal Sex Chromosome Aneuploidy Identified by Non-Invasive Prenatal Testing in 45773 Cases

10.21203/rs.3.rs-39576/v1 ◽

2020 ◽

Author(s):

Xinran Lu ◽

Chaohong Wang ◽

Yuxiu Sun ◽

Junxiang Tang ◽

Keting Tong ◽

...

Keyword(s):

Prenatal Diagnosis ◽

High Risk ◽

Pregnant Women ◽

Maternal Age ◽

Sex Chromosome ◽

Karyotype Analysis ◽

Prenatal Testing ◽

Sex Chromosome Aneuploidy ◽

Non Invasive ◽

Chromosome Aneuploidy

Abstract Objective: To investigate the positive predictive value (PPV) and clinical features of non-invasive prenatal testing (NIPT) as a screening method in detecting sex chromosome aneuploidy (SCA) within a high-risk population at the Maternity and Child Health Hospital of Anhui Province.Methods: From June 2015 to June 2019, 45773 women with singleton pregnancies volunteered to take an NIPT. Cell-free fetal DNA was extracted for high-throughput sequencing and amniocentesis karyotype analysis was performed in pregnant women. Results: 314 high-risk pregnant women underwent NIPT and 143 chose invasive prenatal diagnosis. Karyotype analysis was performed in amniotic fluid cells, wherein 7 cases of 45,X (PPV: 12.50%), 16 cases of 47,XXX (PPV: 55.17%), 25 cases of 47,XXY (PPV: 71.43%), and 10 cases of 47,XYY(PPV: 76.92%) were confirmed. The PPV of NIPT for SCA was 40.56%. The rate of SCA detected in women aged 40 years and older was 0.39%, which was significantly different from that detected in women aged <30, 30–34, and 35–39 years (P < 0.05). The detection rates of 47,XXX and 47,XXY were significantly correlated with maternal age (P < 0.05), but those of 45,X and 47,XYY showed no significant correlation with maternal age.Conclusion: NIPT can be applied for the detection of SCA, but the detection accuracy is low. Genetic counseling and further prenatal diagnosis should be provided.

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